The proposed research represents a multifaceted approach to elucidate the functional relationship between the substantia nigra and the striatum. In these experiments, rather than attempting to directly study the processing of information within each of the structures, we intend to concentrate on the outputs of the nigra and striatum, with special emphasis on the nigrostriatal dopaminergic projection, as well as the efferent connections to other brain regions. All studies will be done in the rat. The experimental approach includes the measurement of behavioral responses to brain stimulation, electrophysiological studies of single neurons, and the effects, on both behavioral and electrophysiological responses, of drugs which influence synaptic transmission. Of particular pharmacological interest are drugs which either enhance or inhibit transmission at dopaminergic and cholinergic synapses. Studies will be done in intact rats and in rats with selective electrolytic and neurochemical brain lesions. Numerous diseases are characterized by nigral and/or striatal pathology, the two most prominent being Parkinson's Disease and Huntington's Chorea. Drug induced diskinesias such as phenothiazine induced Parkinsonism and tardive dyskinesias also reflect alterations in striatal function. The greater our knowledge of the functions of the nigra and striatum and their interrelationship, the closer we come to effectively ameliorating the symptoms of the degenerative diseases, and eliminating the iatrogenic ones.